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We assessed age-specific CD4 T-cell counts and their determinants among Tanzanian children born to HIV-infected mothers to address a major research gap. A total of 474 HIV-uninfected and 69 HIV-infected children were followed until age of 12 months. Maternal predictors were measured during pregnancy and child predictors at birth and throughout the follow up. Child CD4 T-cell counts were evaluated at the age of 3 months and subsequent 3-month intervals; they decreased linearly among HIV-infected (β=–8 cells per week; 95% CI –12 to –4; P=0.0003) and increased linearly among HIV-uninfected children (β=4 cells/week; 95% CI 2–7; P=0.0008). Decreased child counts were predicted by low child anthropometry, maternal HIV stage ≥2, and maternal mid-upper arm circumference <27 cm among HIV-infected children; and by weight-for-height <–2 z-score, maternal HIV stage ≥2, maternal erythrocyte sedimentation rate <81 mm/h and maternal haemoglobin <8.5 g/dl among HIV-uninfected children. The maternal and child predictors described may serve as intervention targets among HIV-exposed children.